Various publications, including patents, published applications, technical articles and scholarly articles are cited throughout the specification. Each of these cited publications is incorporated by reference herein, in its entirety and for all purposes.
Lung cancer is a leading cause of cancer death in the United States and has surpassed breast cancer as the primary cause of cancer-related mortality in women. Exposure to tobacco smoke is estimated to account for approximately 90% of all lung cancers. Women appear to have an increased susceptibility to tobacco carcinogens but have a better prognosis after lung cancer diagnosis as compared with men. Estrogens may affect the susceptibility of women to lung cancer.
Head and neck cancer, currently the sixth most common cancer in the U.S., accounts for 650,000 new cancer cases each year worldwide. Head and neck cancer is a heterogeneous group of malignancies that develop primarily in the squamous epithelium of the lip, oral cavity, pharynx, larynx, nasal cavity, and paranasal sinuses. A rise in the incidence of squamous cell carcinoma (SCC) of the head and neck (HNSCC) in adults age 40 or less has been reported and attributed primarily to an increase in the prevalence of tongue cancers.
Exposure to tobacco smoke is among the major risk factors for developing lung cancer or HNSCC. It is well documented that the majority of non-smoking and non-drinking lung cancer patients are females. Recent data suggest that 75% of young, non-smoker/non-drinker HNSCC patients who develop oral tongue SCC (not associated with human papilloma virus infection) are female. Thus, in addition to the major risk factors, female hormones may contribute to head and neck carcinogenesis.
CYP1B1 is an enzyme that, along with CYP1A1 and CYP3A4, catalyzes the formation of carcinogenic metabolites of 17β-estradiol (E2) and of constituents of tobacco smoke that are subsequently inactivated by one or more detoxification enzymes, including catechol-o-methyltransferase (COMT), sulfotransferase (SULT)1A1, UDP-glucuronosyltransferase (UGT)1A1 and glutathione-S-transferase (GST)P1.
There is a need for additional treatments for head and neck cancers and for lung cancers, including chemopreventive therapies.